Ketone bodies and fatty acids serve as principal energy sources for heart; however, at the level of ketone bodies achieved in uncontrolled diabetes, ketone bodies are used in preference to fatty acids. A large proportion of fatty acid taken up by heart under these conditions becomes esterified in triglyceride. In addition ketone bodies, directly or indirectly, inhibit mobilization of heart triglyceride. This research is directed at understanding how the metabolism of ketone bodies and fatty acids are linked in heart. Studies are being conducted at both the enzyme level and at the organ level using isolated perfused heart. To date the kinetic and regulatory properties of the acyl CoA dehydrogenase have been investigated. Significantly acetoacetyl CoA in intermediate in ketone body oxidation has been found to be a potent inhibitor of the dehydrogenase at concentrations below physiological concentrations. The properties of the dehydrogenase-acetoacetyl CoA complex may also have mechanistic implications. Measurement of hear triacylglycerols in genetically obese hyperglycemic (ob/ob) mice showed a 3-fold increase over the corresponding lean controls. In that no increase in plasma triacylglycerols, FFA or ketone bodies was observed ion ob/ob mice, the factor(s) responsible for the elevation in heart triacylglycerols is unclear. Possibly, the hyperglycemia in combination with hyperinsulinemia that characterize the obese mice promote reesterification, diverting fatty acid away from oxidative pathways.